| First Author | Huynh FK | Year | 2020 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 319 |
| Issue | 4 | Pages | E805-E813 |
| PubMed ID | 32865009 | Mgi Jnum | J:296865 |
| Mgi Id | MGI:6469167 | Doi | 10.1152/ajpendo.00170.2020 |
| Citation | Huynh FK, et al. (2020) beta-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice. Am J Physiol Endocrinol Metab 319(4):E805-E813 |
| abstractText | Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 [SIRT4-knockout (KO) mice] developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance. Because whole body SIRT4-KO mice had alterations to nutrient-stimulated insulin secretion, we hypothesized that SIRT4 plays a direct role in regulating pancreatic beta-cell function. Thus, we tested whether beta-cell-specific ablation of SIRT4 would recapitulate the elevated insulin secretion seen in mice with a global loss of SIRT4. Tamoxifen-inducible beta-cell-specific SIRT4-KO mice were generated, and their glucose tolerance and glucose- and leucine-stimulated insulin secretion were measured over time. These mice exhibited normal glucose- and leucine-stimulated insulin secretion and maintained normal glucose tolerance even as they aged. Furthermore, 832/13 beta-cells with a CRISPR/Cas9n-mediated loss of SIRT4 did not show any alterations in nutrient-stimulated insulin secretion. Despite the fact that whole body SIRT4-KO mice demonstrated an age-induced increase in glucose- and leucine-stimulated insulin secretion, our current data indicate that the loss of SIRT4 specifically in pancreatic beta-cells, both in vivo and in vitro, does not have a significant impact on nutrient-stimulated insulin secretion. These data suggest that SIRT4 controls nutrient-stimulated insulin secretion during aging by acting on tissues external to the beta-cell, which warrants further study. |
